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Parasitol Res (2002) 88: 1040–1043

DOI 10.1007/s00436-002-0712-6


Jean-François Faucher Æ Edouard Ngou-Milama

Michel Anoumou Missinou Æ Raphaël Ngomo
Maryvonne Kombila Æ Peter G. Kremsner

The impact of malaria on common lipid parameters

Received: 2 April 2002 / Accepted: 10 June 2002 / Published online: 23 July 2002
Ó Springer-Verlag 2002

Abstract No data are available in the literature to in- needed to explore the relevance of this finding at the
dicate whether low-level Plasmodium falciparum infec- population level in hyperendemic malaria areas.
tions induce lipid parameter changes. We hypothesized
that low-level P. falciparum infections induce significant
changes in common lipid parameters. We retrospectively
selected samples from a malaria prophylaxis study to Introduction
measure the impact of sustained parasite clearance on
common lipid parameters [total cholesterol (TChol), Very little is known about lipid changes related to ma-
high-density lipoprotein (HDL)-cholesterol (HDL-c), laria. Hypocholesterolemia and hypertriglyceridemia
low-density lipoprotein (LDL)-cholesterol (LDL-c) and were observed in the setting of both uncomplicated and
triglycerides (TG)] in 47 apparently healthy schoolchil- complicated malaria (Das et al. 1996; Davis et al. 1993;
dren whose P. falciparum parasitemia was initially below Mohanty et al. 1992; Nilsson-Ehle and Nilsson-Ehle
1000/ll. After parasite clearance, mean values were 1990; Ngou-Milama et al. 1995) and in the setting of
significantly increased for Tchol (P<0.001) and HDL-c many other acute infections (Bentz and Magnette 1998;
(P<0.001), unlike LDL-c (P=0.93); and TG were sig- Samra et al. 1996). The magnitude of these changes
nificantly decreased from the baseline (P=0.004). No seems related to the severity of malaria (Das et al. 1996;
significant change was found in a control group. This is Mohanty et al. 1992). In one study conducted in non-
the first study showing significant lipid changes related immune patients, however, no correlation was found
to low-level P. falciparum infections. Further studies are between the severity of malaria attacks and the extent of
high-density lipoprotein (HDL)-cholesterol decrease
(Kittl et al. 1992).
Population studies on common lipid parameters
J.-F. Faucher (&) indicate that cholesterol values are currently lower in
Service des Maladies Infectieuses et Tropicales, Africa, where malaria is endemic, than in many other
Hôpital St Jacques, CHU de Besançon,
25030 Besançon cedex, France
parts of the world (Brotons et al. 1997). Thus, yet
E-mail: unknown genetic and environmental factors take part in
Tel.: +33-381-218533 the trend to cholesterol decrease in Africa and are
Fax: +33-381-218772 therefore to be studied. The impact of environmental
J.-F. Faucher Æ M.A. Missinou Æ P.G. Kremsner factors on cholesterolemia is illustrated by the rise in
Medical Research Unit, Albert Schweitzer Hospital, cholesterolemia observed in Africans living in urban
Lambaréné, Gabon centers, in comparison to Africans living traditionally in
E. Ngou-Milama Æ R. Ngomo rural areas (Walker and Sareli 1997). Environmental
Laboratoire de Biochimie, Faculté de Médecine et des factors include lifestyle changes and changes in the
Sciences de la Santé, Libreville, Gabon
prevalence of infections, the main one being malaria.
M.A. Missinou Æ P.G. Kremsner Evaluating the impact of malaria on lipid parameters at
Department of Parasitology, the population level is a difficult challenge. At any given
Institute for Tropical Medicine, University of Tübingen,
Tübingen, Germany time, low-level Plasmodium falciparum parasitemia is
highly prevalent in areas hyperendemic for malaria.
M. Kombila
Laboratoire de Parasitologie,
However, no data are available in the literature to in-
Faculté de Médecine et des Sciences de la Santé, dicate whether lipid parameter changes are related to this
Libreville, Gabon condition. We hypothesized that low-level P. falciparum

infections induce significant changes in common lipid Statistical analysis

parameters. We designed a retrospective analysis of
Statistical analysis was done with Statview software (SAS Insti-
plasma samples obtained while performing a malaria tute). Differences between D0 data and D35 data for each pa-
prophylaxis study, in order to explore the role played by rameter were assessed using the Wilcoxon signed rank test. The P
low level parasitemia on common lipid parameters in values given are two-sided.
Gabonese children attending school.

Materials and methods
Of the total 330 volunteers, 112 (34%) had a positive
Samples were retrospectively selected from a prophylaxis study on blood smear at the start of clearance treatment: 107 had
atovaquone-proguanil (A-P; Malarone, Glaxo Wellcome, Becken- Plasmodium falciparum (median = 620/ll), 3 had
ham, UK) which took place in the Lalala Public school in P. malariae and 2 had P. ovale. A total of 58 chidren
Lambaréné, Gabon, between January and June 2000. Lambaréné is
in the tropical rain forest in an area hyperendemic for Plasmodium (18% of volunteers) had a P. falciparum parasitemia
falciparum malaria (Wildling et al. 1995); and the parasites in this below 1000/ll. Among these children, 47 (21 allocated
region are resistant to chloroquine (Kremsner et al. 1994). Healthy to receive a placebo, 26 allocated to receive A-P) both
schoolchildren aged 4–16 years, who did not receive drugs with cleared parasitemia within 7 days and remained negative
antimalarial activity within 7 days before enrolment in the trial,
participated in screening. We assessed baseline health by a medical
for at least 6 weeks (median = 120/ll).
examination. Written informed consent was obtained from the Among the total volunteers, 218 (66%) had a nega-
parents of the children. The study was approved by the ethics tive blood smear at the start of clearance treatment; and
committee of the International Foundation of the Albert 194 remained negative for at least 6 weeks. In this
Schweitzer Hospital in Lambaréné. group, we randomly selected samples from 21 volunteers
At baseline screening, we collected venous blood samples for
hematological and clinical chemistry tests and if appropriate, for a allocated to receive a placebo and 26 allocated to receive
pregnancy test. Because we expected a high rate of parasitemia in A-P.
these children at baseline, all the children received an initial cu- Table 1 shows the demographic and laboratory
rative treatment course of artesunate (Plasmotrim Lactab, Me- characteristics of volunteers from groups LP and C at
pha) once daily for 3 days. A thick blood smear was taken at the
start and at the end of this initial curative treatment course. The study enrolment.
smears were stained with Giemsa stain and parasite counts were In the LP group (Table 2), from D0 until D35, a
measured as previously described, with a detection limit that highly significant increase in both Tchol (P<0.001) and
corresponded to 5 parasites/ll (Kremsner et al. 1988). For the HDL-c (P<0.001) values were observed, while LDL-c
chemosuppression phase, volunteers received a placebo or a daily
dose of A-P. Thick blood smears were taken weekly. The
values did not change (P=0.93). TG values decreased
chemosuppression phase began 7 days after the initial treatment significantly between D0 and D35 (P=0.005).
and continued for 12 weeks. Blood samples were again collected In the C group (Table 3), there was no significant
5 weeks after the initial clearance treatment in all children re- change between D0 and D35 for Tchol (P=0.6), HDL-c
maining in the study. (P=0.05), LDL-c (P= 0.17) and TG (P=0.26).
A further analysis was performed in a subset of the
Sample selection 47 children of the LP group, restricted to 21 healthy
schoolchildren whose P. falciparum parasitemia was
Plasma was obtained for each child at the start of clearance initially below 100/ll [very low parasitemia (VLP)
treatment (D0) and 5 weeks later (D35). Since all chidren received group]. In the VLP group, mean values on D35 were
at least one study drug (artesunate) and in order to rule out a study
drugs-induced effect on lipids parameters, we selected two sets of significantly increased for Tchol (P=0.03) and HDL-c
samples according to the following criteria:
1. Low parasitemia (LP) group : (1) a positive P. falciparum par- Table 1. Demographic and laboratory characteristics of volunteers
asitemia below 1000 parasites/ll at the start of clearance treat- in the low parasitemia (LP) and control (C) groups at enrolment in
ment followed by parasite clearance within 7 days and (2) a a prophylaxis trial comparing atovaquone-proguanil (A-P) against
further negativity of weekly thick blood smears during 6 weeks. a placebo. In the LP group, the male:female ratio for the total
2. Control (C) group: (1) A negative P. falciparum parasitemia at 107 children with an initial Plasmodium falciparum positive smear
the start of clearance treatment and (2) a further negativity of was 60:47. In the C group, the male:female ratio for the total
weekly thick blood smears during 6 weeks. Because the number 218 children with a initially negative smear was 89:129. In both
of such samples largely exceeded the number of group LP groups, the A-P:placebo ratio was 1.24:1.00 (26:21). Values given
samples and for logistic reasons, we randomly selected a number are means (±SD)
of samples that was equal to the LP group samples (see Results)
in each treatment group (A-P, placebo). LP group C group
(47 children) (47 children)

Male:female (n) 25:22 20:27

Sample analysis Age (years) 9.1 (±2.7) 8.9 (±2.3)
Weight (kg) 26 (±7) 25 (±7)
Each of the common lipid parameters [total cholesterol (Tchol), Hb (g/dl) 10.2 (±1.4) 10.9 (±1.1)
HDL-cholesterol (HDL-c), low-density lipoprotein (LDL)-choles- Creatinine (lmol/l) 66.0 (±6.6) 67.0 (±9.5)
terol (LDL-c) and triglycerides (TG)] was measured using a ALAT (units/ll) 30 (±10) 34 (±23)
Biomérieux kit and an enzymatic procedure on an autoanalyser Bilirubin (units/ll) 16.0 (±8.1) 14.0 (±8.1)
RA 1000 System.